Department of International Health, University of Copenhagen, Copenhagen, Denmark.
J Immunol. 2010 Aug 1;185(3):1730-43. doi: 10.4049/jimmunol.0903894. Epub 2010 Jul 2.
Lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cell responses are considered to be independent of CD28-B7 costimulation. However, the LCMV-specific response has never been evaluated in B7.1/B7.2(-/-) mice. For this reason, we decided to study the T cell response in B7.1/B7.2(-/-) mice infected with two different strains of LCMV, one (Traub strain) typically causing low-grade chronic infection, and another (Armstrong clone 53b) displaying very limited capacity for establishing chronic infection. Using Traub virus we found that most B7.1/B7.2(-/-) mice were unable to rid themselves of the infection. Chronic infection was associated with a perturbed CD8(+) T cell epitope hierarchy, as well as with the accumulation of cells expressing markers of terminal differentiation and being unable to respond optimally to Ag restimulation. Examination of matched CD28(-/-) mice revealed a similar albeit less pronounced pattern of CD8(+) T cell dysfunction despite lack of virus persistence. Finally, analysis of B7.1/B7.2(-/-) mice infected with Armstrong virus revealed a scenario quite similar to that in Traub infected CD28(-/-) mice; that is, the mice displayed evidence of T cell dysfunction, but no chronic infection. Taken together, these results indicate that B7 costimulation is required for induction and maintenance of LCMV-specific CD8(+) T cell memory, irrespective of the LCMV strain used for priming. However, the erosion of CD8(+) T cell memory in B7.1/B7.2(-/-) mice was more pronounced in association with chronic infection. Finally, virus-specific T cell memory was more impaired in the absence of B7 molecules than in the absence of the CD28 receptor, supporting earlier data suggesting the existence of additional stimulatory receptors for B7.
淋巴细胞性脉络丛脑膜炎病毒 (LCMV)-特异性 CD8(+) T 细胞反应被认为独立于 CD28-B7 共刺激。然而，从未在 B7.1/B7.2(-/-) 小鼠中评估过 LCMV 特异性反应。出于这个原因，我们决定研究感染两种不同 LCMV 株的 B7.1/B7.2(-/-) 小鼠中的 T 细胞反应，一种（Traub 株）通常导致低度慢性感染，另一种（Armstrong 克隆 53b）显示出建立慢性感染的能力非常有限。使用 Traub 病毒，我们发现大多数 B7.1/B7.2(-/-) 小鼠无法摆脱感染。慢性感染与 CD8(+) T 细胞表位层次结构的紊乱有关，以及与表达终末分化标志物的细胞的积累以及无法对 Ag 再刺激做出最佳反应有关。对匹配的 CD28(-/-) 小鼠的检查显示出类似的但不太明显的 CD8(+) T 细胞功能障碍模式，尽管没有病毒持续存在。最后，分析感染 Armstrong 病毒的 B7.1/B7.2(-/-) 小鼠显示出与 Traub 感染的 CD28(-/-) 小鼠非常相似的情况；也就是说，小鼠显示出 T 细胞功能障碍的证据，但没有慢性感染。总之，这些结果表明，B7 共刺激对于诱导和维持 LCMV 特异性 CD8(+) T 细胞记忆是必需的，无论用于启动的 LCMV 株如何。然而，B7.1/B7.2(-/-) 小鼠中的 CD8(+) T 细胞记忆的侵蚀在与慢性感染相关时更为明显。最后，在缺乏 B7 分子的情况下，病毒特异性 T 细胞记忆的损伤比在缺乏 CD28 受体的情况下更为严重，这支持了早期数据表明存在用于 B7 的其他刺激受体。
